Sequence-dependent co-condensation of Lsr2 with DNA elucidates the mechanism of genome compaction in Mycobacterium tuberculosis.

ABSTRACT: The xenogeneic silencer protein Lsr2 from Mycobacterium tuberculosis plays a critical role in its survival and pathogenesis. Lsr2 is a nucleoid-associated protein (NAP) that interacts with DNA in vivo and regulates many genes. Purified Lsr2 forms nucleoprotein filaments with DNA molecules, leading to highly compacted DNA conformations. However, the physical mechanism underlying Lsr2-mediated DNA compaction, resulting in gene regulation, remains elusive. We employed a combination of biochemical assay, single-molecule imaging, and molecular dynamics simulations to investigate the governing principles of Lsr2-mediated DNA compaction. We show that, while Lsr2 alone undergoes phase separation, addition of DNA substantially lowers the required concentration for its phase separation. Strikingly,

SUBMITTER: Gaur P 

PROVIDER: S-EPMC12781881 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature